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Mechanisms of Ageing and Development Jan 2019Ageing is today a major societal concern that is intrinsically associated with the increase of life expectancy. Outside the context of severe degenerative diseases that... (Review)
Review
Ageing is today a major societal concern that is intrinsically associated with the increase of life expectancy. Outside the context of severe degenerative diseases that affect the elderly populations, normal visible signs of ageing, notably skin sagging and wrinkles, influence the social and individual perception of peoples. Accordingly, there is a strong demand for researches on skin ageing. Deciphering the cellular and molecular processes of skin evolution through ageing is thus an active scientific domain, at the frontier of tissue developmental and ageing biology. The focus of the present article is to provide an overview of the current knowledge concerning the evolution of dermis characteristics at different life stages, from intra-uterine to post-natal life. The description will integrate stage-specific and age-related changes in dermis characteristics at the tissue, cell, and molecular levels.
Topics: Aging; Animals; Dermis; Extracellular Matrix; Humans; Skin Aging
PubMed: 29548941
DOI: 10.1016/j.mad.2018.03.006 -
Seminars in Neonatology : SN Nov 2000All the dermal structures are less well developed in the newborn than in the older infant or child, but there are few important consequences of this. Sweating in... (Review)
Review
All the dermal structures are less well developed in the newborn than in the older infant or child, but there are few important consequences of this. Sweating in response to a thermal stimulus occurs at birth in the term infant and can be detected in most preterm infants from 2 weeks of age. It is poorly developed though. Emotional (palmar/plantar) sweating is present from birth in term infants only. Skin blood flow can be regulated in term and preterm infants, and is often measured indirectly as a temperature gradient. Such a gradient is temperature as well as illness dependent which limits its use as a clinical tool. Sensory nerve endings are readily stimulated in the most immature infants. Finally, damage to the skin in the newborn period commonly leads to scarring, although this usually improves with time.
Topics: Dermis; Emotions; Humans; Hypohidrosis; Infant, Newborn; Skin; Sweating; Wound Healing
PubMed: 11032713
DOI: 10.1053/siny.2000.0016 -
The Journal of Clinical Investigation Jan 2018Fibroblasts synthesize the extracellular matrix of connective tissue and play an essential role in maintaining the structural integrity of most tissues. Researchers have... (Review)
Review
Fibroblasts synthesize the extracellular matrix of connective tissue and play an essential role in maintaining the structural integrity of most tissues. Researchers have long suspected that fibroblasts exhibit functional specialization according to their organ of origin, body site, and spatial location. In recent years, a number of approaches have revealed the existence of fibroblast subtypes in mice. Here, we discuss fibroblast heterogeneity with a focus on the mammalian dermis, which has proven an accessible and tractable system for the dissection of these relationships. We begin by considering differences in fibroblast identity according to anatomical site of origin. Subsequently, we discuss new results relating to the existence of multiple fibroblast subtypes within the mouse dermis. We consider the developmental origin of fibroblasts and how this influences heterogeneity and lineage restriction. We discuss the mechanisms by which fibroblast heterogeneity arises, including intrinsic specification by transcriptional regulatory networks and epigenetic factors in combination with extrinsic effects of the spatial context within tissue. Finally, we discuss how fibroblast heterogeneity may provide insights into pathological states including wound healing, fibrotic diseases, and aging. Our evolving understanding suggests that ex vivo expansion or in vivo inhibition of specific fibroblast subtypes may have important therapeutic applications.
Topics: Animals; Dermis; Epigenesis, Genetic; Fibroblasts; Gene Expression Regulation, Neoplastic; Humans; Skin Neoplasms; Transcription, Genetic
PubMed: 29293096
DOI: 10.1172/JCI93555 -
Dermatologic Clinics Jan 2017Human skin wounds heal largely by reparative wound healing rather than regenerative wound healing. Human skin wounds heal with scarring and without pilosebaceous units... (Review)
Review
Human skin wounds heal largely by reparative wound healing rather than regenerative wound healing. Human skin wounds heal with scarring and without pilosebaceous units or other appendages. Dermal fibroblasts come from 2 distinct lineages of cells that have distinct cell markers and, more importantly, distinct functional abilities. Human skin wound healing largely involves the dermal fibroblast lineage from the reticular dermis and not the papillary dermis. If scientists could find a way to stimulate the dermal fibroblast lineages from the papillary dermis in early wound healing, perhaps human skin wounds could heal without scarring and with skin appendages.
Topics: Cicatrix; Dermis; Fibroblasts; Hair Follicle; Humans; Regeneration; Sebaceous Glands; Skin; Sweat Glands; Wound Healing
PubMed: 27890241
DOI: 10.1016/j.det.2016.07.004 -
Wiley Interdisciplinary Reviews.... Mar 2018The skin is the largest organ of the body and is composed of two layers: the overlying epidermis and the underlying dermis. The dermal fibroblasts originate from... (Review)
Review
The skin is the largest organ of the body and is composed of two layers: the overlying epidermis and the underlying dermis. The dermal fibroblasts originate from distinct locations of the embryo and contain the positional identity and patterning information in the skin. The dermal fibroblast progenitors differentiate into various cell types that are fated to perform specific functions such as hair follicle initiation and scar formation during wound healing. Recent studies have revealed the heterogeneity and plasticity of dermal fibroblasts within skin, which has implications for skin disease and tissue engineering. The objective of this review is to frame our current understanding and provide new insights on the origin and differentiation of dermal fibroblasts and their function during cutaneous development and healing. WIREs Dev Biol 2018, 7:e307. doi: 10.1002/wdev.307 This article is categorized under: Birth Defects > Organ Anomalies Signaling Pathways > Cell Fate Signaling Adult Stem Cells, Tissue Renewal, and Regeneration > Regeneration Nervous System Development > Vertebrates: Regional Development.
Topics: Animals; Cell Differentiation; Cicatrix; Dermis; Embryonic Stem Cells; Fibroblasts; Humans
PubMed: 29244903
DOI: 10.1002/wdev.307 -
International Journal of Molecular... May 2022Skin aging is a multi-factorial process that affects nearly every aspect of skin biology and function. The processes developing in the skin during aging are based on... (Review)
Review
Skin aging is a multi-factorial process that affects nearly every aspect of skin biology and function. The processes developing in the skin during aging are based on fundamental molecular mechanisms associated with fibroblasts, the main cellular population of the dermis. It has been revealed that the amount of fibroblasts decreases markedly with age and their functional activity is also reduced. This inevitably leads to a decrease in the regenerative abilities of the skin and the progression of its aging. In this review we consider the mechanisms underlying these processes, mainly the changes observed with age in the stem/progenitor cells that constitute the fibroblastic differon of the dermis and form their microenvironment (niches). These changes lead to the depletion of stem cells, which, in turn, leads to a decrease in the number of differentiated (mature) dermal fibroblasts responsible for the production of the dermal extracellular matrix and its remodeling. We also describe in detail DNA damages, their cellular and systemic consequences, molecular mechanisms of DNA damage response, and also the role of fibroblast senescence in skin aging.
Topics: Dermis; Extracellular Matrix; Fibroblasts; Skin; Skin Aging
PubMed: 35682813
DOI: 10.3390/ijms23116135 -
Nature Dec 2013Fibroblasts are the major mesenchymal cell type in connective tissue and deposit the collagen and elastic fibres of the extracellular matrix (ECM). Even within a single...
Fibroblasts are the major mesenchymal cell type in connective tissue and deposit the collagen and elastic fibres of the extracellular matrix (ECM). Even within a single tissue, fibroblasts exhibit considerable functional diversity, but it is not known whether this reflects the existence of a differentiation hierarchy or is a response to different environmental factors. Here we show, using transplantation assays and lineage tracing in mice, that the fibroblasts of skin connective tissue arise from two distinct lineages. One forms the upper dermis, including the dermal papilla that regulates hair growth and the arrector pili muscle, which controls piloerection. The other forms the lower dermis, including the reticular fibroblasts that synthesize the bulk of the fibrillar ECM, and the preadipocytes and adipocytes of the hypodermis. The upper lineage is required for hair follicle formation. In wounded adult skin, the initial wave of dermal repair is mediated by the lower lineage and upper dermal fibroblasts are recruited only during re-epithelialization. Epidermal β-catenin activation stimulates the expansion of the upper dermal lineage, rendering wounds permissive for hair follicle formation. Our findings explain why wounding is linked to formation of ECM-rich scar tissue that lacks hair follicles. They also form a platform for discovering fibroblast lineages in other tissues and for examining fibroblast changes in ageing and disease.
Topics: Adipocytes; Animals; Cell Lineage; Dermis; Female; Fibroblasts; Hair Follicle; In Vitro Techniques; Male; Mice; Mice, Inbred C57BL; Mice, Inbred CBA; Mice, Transgenic; Muscle, Smooth; Skin; Wound Healing; beta Catenin
PubMed: 24336287
DOI: 10.1038/nature12783 -
Theranostics 2021Vascular endothelial cells (ECs) are increasingly recognized as active players in intercellular crosstalk more than passive linings of a conduit for nutrition delivery.... (Comparative Study)
Comparative Study
Vascular endothelial cells (ECs) are increasingly recognized as active players in intercellular crosstalk more than passive linings of a conduit for nutrition delivery. Yet, their functional roles and heterogeneity in skin remain uncharacterized. We have used single-cell RNA sequencing (scRNA-seq) as a profiling strategy to investigate the tissue-specific features and intra-tissue heterogeneity in dermal ECs at single-cell level. Skin tissues collected from 10 donors were subjected to scRNA-seq. Human dermal EC atlas of over 23,000 single-cell transcriptomes was obtained and further analyzed. Arteriovenous markers discovered in scRNA-seq were validated in human skin samples via immunofluorescence. To illustrate tissue-specific characteristics of dermal ECs, ECs from other human tissues were extracted from previously reported data and compared with our transcriptomic data. In comparison with ECs from other human tissues, dermal ECs possess unique characteristics in metabolism, cytokine signaling, chemotaxis, and cell adhesions. Within dermal ECs, 5 major subtypes were identified, which varied in molecular signatures and biological activities. Metabolic transcriptome analysis revealed a preference for oxidative phosphorylation in arteriole ECs when compared to capillary and venule ECs. Capillary ECs abundantly expressed HLA-II molecules, suggesting its immune-surveillance role. Post-capillary venule ECs, with high levels of adhesion molecules, were equipped with the capacity in immune cell arrest, adhesion, and infiltration. Our study provides a comprehensive characterization of EC features and heterogeneity in human dermis and sets the stage for future research in identifying disease-specific alterations of dermal ECs in various dermatoses.
Topics: Base Sequence; Biomarkers; Capillaries; Cell Adhesion; Dermis; Endothelial Cells; Gene Expression; Humans; Phenotype; Single-Cell Analysis; Transcriptome; Venules
PubMed: 33995668
DOI: 10.7150/thno.54917 -
The Journal of Investigative... Aug 1998Cutaneous aging is a complex biological phenomenon consisting of two distinct components, (a) the intrinsic, genetically determined degenerative aging processes and (b)... (Review)
Review
Cutaneous aging is a complex biological phenomenon consisting of two distinct components, (a) the intrinsic, genetically determined degenerative aging processes and (b) extrinsic aging due to exposure to the environment, also known as "photoaging". These two processes are superimposed in the sun-exposed areas of skin, with profound effects on the biology of cellular and structural elements of the skin. This overview summarizes our current understanding of the mechanisms of innate versus extrinsic aging with emphasis on connective tissue alterations, primarily collagen and the elastic fiber network. We also introduce a novel transgenic mouse model, expressing a human elastin promoter-reporter gene construct, suitable for studies on biology and preventive pharmacology of the cutaneous aging.
Topics: Animals; Collagen; Dermis; Elastin; Humans; Mice; Mice, Transgenic; Skin Aging
PubMed: 9732056
DOI: No ID Found -
Acta Biomaterialia Mar 2019Skin, the outermost layer of the body, fulfills a broad range of functions, protecting internal organs from damage and infection, while regulating the body's temperature...
Skin, the outermost layer of the body, fulfills a broad range of functions, protecting internal organs from damage and infection, while regulating the body's temperature and water content via the exchange of heat and fluids. It must be able to withstand and recover from extensive deformation and damage that can occur during growth, movement, and potential injuries. A detailed investigation of the evolution of the collagen architecture of the dermis as a function of deformation is conducted, which reveals new aspects that help us to understand the mechanical response of skin. Juvenile pig is used as a model material because of its similarity to human skin. The dermis is found to have a tridimensional woven structure of collagen fibers, which evolves with deformation. After failure, we observe that the fibers have straightened and aligned in the direction of tension. The effects of strain-rate change, cyclic loading, stress relaxation, and orientation are quantitatively established. Digital image correlation techniques are implemented to quantify skin's anisotropy; measurements of the Poisson ratio are reported. This is coupled with transmission electron microscopy which enables obtaining quantitative strain parameters evaluated through the orientation and curvature of the collagen fibers and their changes, for the first time in all three dimensions of the tissue. A model experiment using braided human hair in tension exhibits a similar J-curve response to skin, and we propose that this fiber configuration is at least partially responsible for the monotonic increase of the tangent modulus of skin with strain. The obtained results are intended to serve as a basis for structurally-based models of skin. STATEMENT OF SIGNIFICANCE: Our study reveals a new aspect of the dermis: it is comprised of a tridimensional woven structure of collagen fibers, which evolves with deformation. This is enabled by primarily two techniques, transmission electron microscopy on three perpendicular planes and confocal images with second harmonic generation fluorescence of collagen, captured at different intervals of depth. After failure, the fibers have straightened and aligned in the direction of tension. Digital image correlation techniques are implemented to quantify skin's anisotropy; measurements of the Poisson ratio are reported. A model experiment using braided human hair in tension exhibits a similar J-curve response to skin, and we propose that this fiber configuration is at least partially responsible for the monotonic increase of the tangent modulus of skin with strain.
Topics: Animals; Dermis; Fibrillar Collagens; Humans; Regression Analysis; Stress, Mechanical; Swine; Tensile Strength
PubMed: 30660003
DOI: 10.1016/j.actbio.2019.01.023